Study population and design
A single-center, prospective, randomized, partly blinded study was conducted with 270 consecutive patients referred for gastroscopy between August 2021 and September 2021. The study was approved by the Institutional Ethics Committee of Beijing Hospital (2021BJYYEC-150-02) and registered in the Chinese Clinical Trial Registry (www.chictr.org.cn; ChiCTR2100049180; Date of registration:24/07/2021). The inclusion criteria were as follows: (1) patients aged ≥ 60 years, (2) American Society of Anesthesiologists (ASA) I–II patients, (3) scheduled to undergo a sedative gastroscopy, (4) patient consented to participate in the trial, signed the informed consent form, and was willing to comply with study requirements. The exclusion criteria were as follows: patients (1) who were allergic to used drugs or had a history of anesthesia-associated adverse events, (2) with mental illness, alcohol or drug abuse, (3) with difficult airway or severe respiratory diseases (obstructive sleep apnea syndrome, mouth opening < 3 cm, limited movement of the neck or jaw, morbid obesity, acute respiratory infections, acute onset of chronic obstructive pulmonary disease, and uncontrolled asthma), (4) who had acute heart failure, unstable angina pectoris, myocardial infarction occurred within 6 months, resting electrocardiograph (ECG) heart rate < 50 beats/min, grade III atrioventricular block, severe arrhythmia, moderate to severe heart valve disease, (5) with liver dysfunction (aspartate aminotransferase and/or alanine aminotransferase ≥ 2.5 upper limit of normal (ULN), total bilirubin ≥ 1.5 ULN), or renal dysfunction (urea or urea nitrogen ≥ 1.5 ULN, serum creatinine > ULN), (6) with uncontrolled blood pressure (sitting systolic blood pressure ≥ 160 mmHg or ≤ 90 mmHg, and/or diastolic blood pressure ≥ 100 mmHg), (7) who required an examination time exceeding 30 min, (8) who had participated in other studies within the previous 30 days, and (9) with an unwillingness or inability to cooperate.
Data Collection And Blinding
Written informed consent was obtained from all the eligible patients. The patients’ basic information (age, sex, height, weight, comorbid diseases, smoking and drinking history, and concomitant medication history) was collected by the outpatient doctor during the anesthesia assessment 3–7 days before the examination. On the day of examination, patients with inclusion criteria were randomly assigned to the MS group(2 ≤ MOAA/S ≤ 4) or the DS group (MOAA/S ≤ 1) using computer-generated random sequences. Randomization was not blinded to the anesthesiologists, data record anesthesia nurses, or endoscopists but blinded to patients and nurses in PACU. Vital signs and adverse events during the examination were recorded by the anesthesia nurse. Evaluation in PACU and satisfaction of endoscopists and patients were recorded by the PACU nurse after the examination.
Study Procedures And Drug Administration
Eight hours of fasting for food and 2 hours of fasting for water was performed before the examination. All patients received basic anesthetic monitoring using a five-lead-electrocardiogram, pulse oximetry, and blood pressure cuff and the end-expiratory carbon dioxide. Supplemental oxygen was delivered to all patients during the procedure via nasal cannula (2 L/min). Before entering the examination room, a peripheral intravenous line was set up.
In MS group, patients received an initial intravenous bolus of 1 µg/kg of fentanyl and 1mg of midazolam. Propofol (0.25–0.5 mg/kg) was administered 2 minutes later to achieve moderate sedation (2 ≤ MOAA/S ≤ 4). Subsequent incremental boluses of 10 to 20mg of propofol were given to perform moderate sedation. If the patient seemed agitated or unable to cooperate under MS, propofol was used to deepen sedation level based on clinical experience. In DS group, patients also received an initial intravenous bolus of 1 µg/kg of fentanyl and 1mg of midazolam. Propofol (1–2 mg/kg) was administered 2 minutes later to achieve deep sedation (MOAA/S ≤ 1). Propofol (0.5 mg/kg) was repeated given to maintain DS. MOAA/S was shown in Appendix 1. After examination, all patients were intravenously injected with flumazenil 0.2 mg for antagonism and transferred to PACU. If the fast-track criteria score[10] reached 14 points, patients could be discharged. If not reach 14 points 1h after examination, patients cannot be discharged and should be transferred to the emergency observation room for observation and treatment.
Outcome Measurements And Definitions
The primary outcome assessed was the PACU stay time, defined as the time from the end of the examination to scoring 14 points using the fast-track criteria (assessments were performed every 2 min in PACU). Recorded the time of scoring 2 points in each of the following areas: level of consciousness, physical activity, hemodynamic stability, respiratory stability, oxygen saturation status, postoperative pain assessment, and postoperative emetic symptoms, shown in Appendix 2.
The secondary outcomes were the (1) total hospital stay time (from hospital admission to discharge home), induction time(from administration to gastroscope insertion), operation time(from gastroscope insertion to withdrawal), (2) retching during procedure(the act of vomiting, without vomit), bucking during procedure (an irritating dry cough during examination), and body movement during procedure (the activity of the trunk and extremities, scored according to the following: 0: no movement; 1: general body movements where hand or foot movements do not affect the examination; 2: severe physical movements where leg or hip movements affect the examination), (3) the satisfaction of the endoscopist and patient (using an 11-point numerical rating scale (NRS), where 0 equals totally unsatisfied, 10 equals completely satisfied), (4) the mean blood pressure, heart rate and blood oxygen saturation (SpO2) (basal values(T1), immediately before gastroscope insertion (T2), 2 min after insertion (T3), 5 min after insertion (T4), at the time of withdrawal (T5), and at the time of discharge (T6)), and (5) sedation-associated adverse events during procedure. [11] Severe sedation-associated adverse events were defined as the need for intensive-care unit admission, intubation, resuscitation and/or death; while minor sedation-associated adverse events included respiratory depression which could be corrected rapidly and hemodynamic fluctuations requiring vasoactive drugs. Respiratory depression was defined as hypoxemia (85%<SpO2 < 90% which could be corrected by mask oxygen inhalation and thrusting the jaw), severe hypoxemia (SpO2 ≤ 85% could be corrected by assisted ventilation). Hypotension was the largest decrease in mean arterial pressure at least 20% from the baseline value. Bradycardia was described as heart rates < 50 beats/min. Tachycardia was described as heart rates > 100 beats/min.
Patients with the following criteria had to be withdrawn: unanticipated examination changes, insufficient MS or DS, requiring deepening of anesthesia, and termination of the procedure by the anesthesiologists and endoscopists because of safety concerns.
Sample Size Estimation
The PACU discharge has been reported to be approximately 20 min with DS for elective outpatient colonoscopies. [8] Meanwhile, our pilot study showed that the PACU stay time in DS group was approximately 20 ± 9 min, and the PACU stay time was shorter in MS group. An equivalence margin of 20% in the recovery times between MS and DS groups was selected by investigator consensus, owing to the lack of literature to inform this decision. Therefore, to attain a significance level of 0.05 and a power of 0.9, each group needed 108 participants (total = 236) to show the equivalence using PASS (version 15.0.5, Kaysville, Utah, USA). A recruitment target of 270 patients was set to account for 15% dropouts and allow sufficient power to analyze secondary outcomes.
Statistical Analysis
All the analyses were performed using SPSS Statistics for Windows (version 24.0, IBM Corp., Armonk, New York, USA). Continuous data were tested using the student’s t-test and summarized as the mean (standard deviation) if the data were normally distributed, or tested with a Wilcoxon Rank sum test and summarized as the median (interquartile ranges) if the data were non-normally distributed. A χ2 test or Fisher’s exact test was used to analyze the categorical data. The analysis of repeated measurement data, such as the heart rate and mean blood pressure, was performed using the analysis of variance for multi-factor repeated measurements. All tests were two-tailed, and a value of P < 0.05 was accepted as significant.